Abstract
With the massive data generated by the Human Microbiome Project, how to transform such data into useful information and knowledge remains challenging. Here, with currently available sequencing information (reference genomes and metagenomes), we have developed a comprehensive microarray, HuMiChip2, for strain-level identification and functional characterization of human microbiomes. HuMiChip2 was composed of 29,467 strain-specific probes targeting 2063 microbial strains/species and 133,924 sequence- and group-specific probes targeting 157 key functional gene families involved in various metabolic pathways and host-microbiome interaction processes. Computational evaluation of strain-specific probes suggested that they were not only specific to mock communities of sequenced microorganisms and metagenomes from different human body sites but also to non-sequenced microbial strains. Experimental evaluation of strain-specific probes using single strains/species and mock communities suggested a high specificity of these probes with their corresponding targets. Application of HuMiChip2 to human gut microbiome samples showed the patient microbiomes of alcoholic liver cirrhosis significantly (p < 0.05) shifted their functional structure from the healthy individuals, and the relative abundance of 21 gene families significantly (p < 0.1) differed between the liver cirrhosis patients and healthy individuals. At the strain level, five Bacteroides strains were significantly (p < 0.1) and more frequently detected in liver cirrhosis patients. These results suggest that the developed HuMiChip2 is a useful microbial ecological microarray for both strain-level identification and functional profiling of human microbiomes.
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Author contribution
ZH, JZ, QT, and Lanjuan Li conceived and designed the study. Jiabao Li, QT, ZS, YC, Juan Li, QZ, and XL performed the research. QT, Jiabao Li, ZS, and Lu Lin analyzed the data. QT, ZH, HW, and JY wrote the manuscript. All authors read and approved the manuscript.
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This work was supported by the Oklahoma Center for the Advancement of Science and Technology (OCAST) through the Oklahoma Applied Research Support (OARS) Project AR11-035, the Fundamental Research Funds for the Central Universities of China (Zhejiang University, 2016QNA4039, 2015QNA4044), and the Open Funding of Zhejiang Provincial Key Laboratory of Health Risk Factors for Seafood (201605), Zhoushan Center for Disease Control and Prevention.
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The authors declare that they have no conflict of interest.
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All human individuals involved in this study were provided with written informed consent, and research was approved by the First Affiliated Hospital of Zhejiang University ethics committee and Institutional Review Broad (IRB). All procedures performed in studies involving human participants were in accordance with the ethical standards of the First Affiliated Hospital of Zhejiang University ethics committee and Institutional Review Broad (IRB) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Qichao Tu and Jiabao Li contributed equally to this work.
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Tu, Q., Li, J., Shi, Z. et al. HuMiChip2 for strain level identification and functional profiling of human microbiomes. Appl Microbiol Biotechnol 101, 423–435 (2017). https://doi.org/10.1007/s00253-016-7910-0
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DOI: https://doi.org/10.1007/s00253-016-7910-0